Clonal expansions in acute EBV infection are detectable in the CD8 and not the CD4 subset and persist with a variable CD45 phenotype

被引:103
作者
Maini, MK
Gudgeon, N
Wedderburn, LR
Rickinson, AB
Beverley, PCL
机构
[1] UCL, Dept Sexually Transmitted Dis, Mortimer Market Ctr, London WC1E 6AU, England
[2] UCL, Dept Immunol, London WC1E 6AU, England
[3] UCL, Dept Mol Pathol, London WC1E 6AU, England
[4] Univ Birmingham, Clin Res Ctr, Inst Canc Studies, Birmingham, W Midlands, England
[5] Edward Jenner Inst Vaccine Res, Compton, Berks, England
关键词
D O I
10.4049/jimmunol.165.10.5729
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We have applied a sensitive global analysis of TCR heterogeneity to compare clonal dynamics of CD4(+) and CD8(+) T cells in acute infectious mononucleosis, Using this approach, we are able to identify a broad representation of the total virus-specific population without the bias of in vitro culture and then to track their phenotype and fate by their unique molecular footprint, We demonstrate a large number of Ag-driven clones using different TCRs in the acute phase, all CD8(+), The diverse large clones generated in the CD8 subset in response to this virus contrast with the complete lack of detectable clonal expansion in the CD4 compartment, Many of the same clones remain detectable in directly ex vivo CD8(+) T cells for at least a year after resolution of infectious mononucleosis, although the clone size is reduced. Thus, memory CDS cells following EBV infection persist at relatively high circulating frequency and represent a subset of the large range of clonotypes comprising the acute effecters, Separation of samples into CD45RA (naive) and CD45RO (memory) fractions shows the accumulation of identical CDR3 region defined clonotypes in both CD45RO and CD45RA fractions and sequencing confirms that dominant long-lived monoclonal expansions can reside in the CD45RA pool.
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页码:5729 / 5737
页数:9
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